The enormous potential of fMRI as a tool for understanding the influences of TBI (Traumatic Brain Injury) on cognitive and motor functioning in humans has begun to be realized as a body of neurocognitive TBI literature has started to emerge (McAllister et al., 1999;2001, Christodoulou et al., 2001). While the consistency in these findings has been encouraging, the validity of conclusions regarding the influences of TBI on brain activation patterns measured by fMRI will be dependent upon better characterizing the wide variability in brain activation patterns observed (Hillary, Steffener, Biswal et al., 2002). The aim of our proposal is to systematically examine and quantify the vascular and neural factors contributing to trauma- related changes in the fMRI signal. To the best of our knowledge, this is the first attempt to comprehensively examine the biophysical, neural, and cognitive contributions to TBI-related differences in fMRI activation. The techniques we propose to develop and utilize here can be implemented by other investigators to accurately isolate hemodynamic changes due to trauma-related (or, indeed, any population-related) differences in neural activity. Because of this, the current proposal provides the opportunity to establish new standards for applying BOLD fMRI to clinical samples.. The present project intends to combine basic science, engineering, and computational issues to specifically elucidate mechanisms (neuronal vs vascular) that results in TBI subjects having altered brain activation in comparison to healthy controls. Results obtained from the noninvasive technique (fMRI) would provide ways to measure a number of relevant physiological factors and characterize them biophysically to understand human brain function with TBI. Methods and techniques developed can also be used to study between two or more different groups.